Effects of Infection with SARS-CoV-2 on the Male and Female Reproductive Systems: A Review.

Coronavirus Disease-2019 (COVID-19) is a rapidly spreading pandemic that began at the end of 2019. COVID-19 is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Reproductive health has always been one of the most important healthcare problems, and the impacts of COVID-19 on the reproductive systems have become an emerging topic. The effects of infection with SARS-CoV-2 on males are more harmful than on females. The outcomes of pregnancy also can show the condition of male and female reproductive system health. The vertical transmission of SARS-CoV-2 significantly affects pregnancy healthy. SARS-CoV-2, antibody, and other factors, such as the decline of lymphocyte counts, and increased erythrocyte sedimentation rate, C-reactive protein, and D-dimer levels, are evidence of SARS-CoV-2 vertical transmission. Angiotensin-converting enzyme 2 (ACE2) is regarded as a virus receptor in the reproductive system. The expression and activity of ACE2 are influenced by sex hormones, especially the male sex hormones. The strength of immunity is crucial to fighting off viral infection. Antibodies against SARS-CoV-2 show different expression in male and female patients, and the antibodies have been regarded as having potential applications in COVID-19 prevention and treatment. This review aims to present the current status of what is known about the involvement of the male and female reproductive systems, as well as the effects on pregnancy health, during infection with SARS-CoV-2, and discusses the implications for future fertility.

[Lycium barbarum polysaccharide reduces testicular spermatogenic injury in Immp2l－/－mice through GPX4 and AIF pathways].

OBJECTIVE: To investigate the protective effect of Lycium barbarum polysaccharide (LBP) against testicular spermatogenic injury in mice with oxidative stress (OS) and its mechanism. METHODS: A unique OS model was made in 1.5-month-old mice with mitochondrial inner membrane-like peptide-2 mutation (Immp2l－/－), which were fed with water (the negative control group) or LBP in water at the concentration of 20 mg/kg (the LBP intervention group), and wild-type Immp2l＋/＋ mice used as normal controls and fed with water only. Then all the mice were sacrificed at 13 months old and the testis tissue harvested for observation of pathological changes by HE staining, measurement of routine semen parameters, and detection of the apoptosis of spermatogenic cells by TUNEL and the expression levels of glutathione peroxidase 4 (GPX4) and apoptosis-inducing factor (AIF) by immunohistochemistry and Western blot. RESULTS: Thinned testicular cortex was observed in the negative controls, with evident vacuolar degeneration and reduced numbers of germ cells and elongated spermatids in the lumen of the seminiferous tubules, but all these pathological changes were improved and the germ cells at different levels orderly arranged in the LBP intervention group. Compared with the normal controls, the mice in the negative control group showed dramatically reduced sperm count (ï¼»72.89 ± 8.28ï¼½ vs ï¼»20.78 ± 1.45ï¼½ ×106, P<0.01) and the percentages of progressively motile sperm (PMS) (ï¼»58.62 ± 6.15ï¼½% vs ï¼»18.37 ± 2.67ï¼½%, P<0.01) and morphologically normal sperm (MNS) (ï¼»65.81 ± 7.69ï¼½% vs ï¼»20.33 ± 3.17ï¼½%, P<0.01) and increased apoptosis of spermatogenic cells (ï¼»1.45 ± 0.43ï¼½% vs ï¼»7.14 ± 0.78ï¼½%, P<0.01). LBP intervention, however, significantly increased the sperm count (ï¼»45.25 ± 3.39ï¼½ ×106, P<0.05), PMS (ï¼»36.34 ± 4.56ï¼½%, P<0.05) and MNS (ï¼»38.72 ± 3.63ï¼½%, P<0.05) and decreased the apoptosis of spermatogenic cells (ï¼»2.28 ± 0.07ï¼½%, P<0.01). The mice in the LBP intervention group, in comparison with the negative controls, exhibited remarkably up-regulated expression of GPX4 (2.75 ± 0.48 vs 1.43 ± 0.17, P<0.05) and down-regulated expression of AIF (2.43 ± 0.15 vs 1.35 ± 0.51, P<0.05). CONCLUSIONS: Lycium barbarum polysaccharide at 20 mg/kg can reduce testicular spermatogenic injury in Immp2l－/－ mice with oxidative stress through GPX4 and AIF pathways.

[A review of clinical specifications of Scutellariae Radix pieces in ancient and modern literature].

Scutellariae Radix is a commonly used Chinese medicinal first recorded in the Shennong's Classic of Materia Medica. In the ancient books of traditional Chinese medicine(TCM), Scutellariae Radix is used in two specifications, solid one(Ziqin) and hollow one(Kuqin). In the current rules and regulations of Chinese medicine, Scutellariae Radix is used without the specific requirements for the specifications applied. To clarify the evolution of Scutellariae Radix specifications and analyze the current specifications of Scutellariae Radix pieces, the present study reviews the Scutellariae Radix from ancient literature, modern rules and regulations, and differences between Ziqin and Kuqin in composition, efficacy, and transformation mechanism. According to the research on ancient books, Kuqin is effective in clearing the fire of the upper energizer, and Ziqin in purging the heat of the lower energizer. Modern studies have revealed that Kuqin and Ziqin are significantly different in chemical components, and Ziqin and Kuqin target the colon and lung, respectively, which are consistent with the relevant records in ancient books. The review study suggests that the two specifications of Scutellariae Radix are reasonable since they can facilitate the precise treatment of Scutellariae Radix.

The Association of Partial Azoospermia Factor C Deletions and Male Infertility in Northwestern China.

BACKGROUND: Male infertility is a major health issue worldwide. Y chromosome microdeletions are well-characterized genetic causes of male infertility. The association of partial AZFc deletions (gr/gr, b2/b3, and b1/b3) with male infertility is not well confirmed in diverse populations. The purpose of the present study was to investigate the frequency of partial AZFc deletions and their association with male infertility in a population from Northwestern China. METHODS: Multiplex polymerase chain reaction was used to detect partial AZFc deletions in 228 infertile patients. We analyzed 141 cases of azoospermia (AS), 87 cases of oligozoospermia (OS), and 200 fertile controls. RESULTS: Our data showed that the frequency of a b2/b3 deletion in infertile men, men with AS, men with OS, and controls was 3.51, 2.13, 5.75, and 0.00%, respectively. The frequency of this deletion was significantly different between the infertile group and the control group (3.51 vs. 0.00%, respectively, p = 0.021) and between the OS group and the control group (5.75 vs. 0.00%, respectively, p = 0.003). The frequency of a gr/gr deletion in each group was 11.84, 9.22, 16.09, and 7.50%, respectively. The frequency of a gr/gr deletion was significantly different between the OS group and the control group (16.09 vs. 7.50%, respectively, p = 0.026) but not between the infertile group and the control group (11.84 vs. 7.50%, p = 0.132) or the AS group and the control group (9.22 vs. 7.50%, p = 0.569). The frequency of a b1/b3 deletion was 0.44, 0.71, 0.00, and 3.00%, respectively. For this deletion, there was no significant difference between the infertile (0.44 vs. 3.00%, p = 0.089), AS (0.71 vs. 3.00%, p = 0.276), and OS groups (0.00 vs. 3.00%, p = 0.236) and the control group. CONCLUSIONS: Our results suggest that the b2/b3 deletion might be associated with male infertility and that the gr/gr deletion might be associated with spermatogenic failure in men with OS in Northwestern China (Ningxia).

Lycium barbarum polysaccharide protects against ethanol-induced spermiotoxicity and testicular degeneration in Immp2l+/- mice.

Studies have indicated that high levels of ethanol exposure impaired spermatogenesis in mice. However, the effects of chronic and low-dose alcohol consumption on susceptible populations remain unclear. The previous studies have confirmed that Immp2l mutant mice (Immp2lTg(Tyr)979Ove or Immp2l-/- ) suffered from increased levels of oxidative stress(OS) and male infertility, heterozygous lmmp2l mice (Immp2l+/- ) showed no altered ROS levels under physiological condition. Lycium barbarum polysaccharide (LBP) significantly scavenge oxygen free radicals and enhance antioxidant enzyme activity. The objectives of present study were to research the effects of chronic and low-dose alcohol-induced damage on Immp2l+/- , explore the protective function of LBP and possible mechanism. The results indicated that chronic ethanol exposure leads to spermatogenic impairment and triggered a toxic effect on germ cell, 10 mg/kg LBP administration improved the quality of spermatozoon, decreased the ratio of apoptotic germ cells and the expression of Col1a1 and Col1a2, while increased the level of TNP2 and RPL31. In conclusion, the study may provide basic knowledge about LBP's important role against ethanol-induced spermiotoxicity and testicular degeneration in Immp2l+/- mice, and the mechanism may be that LBP influenced the state of the spermatogenic epithelium by decreasing the expression of Collagen level leading to alterations in protein biosynthesis during the process of spermatogenesis.

[Identification of a novel c.1A>G variant of GDAP1 gene in a pedigree affected with autosomal recessive fibula atrophy].

OBJECTIVE: To explore the genetic basis for a pedigree affected with Charcot-Marie-Tooth (CMT) disease through high-throughput sequencing. METHODS: Potential variants of the genes associated with CMT were screened by next-generation sequencing (NGS) of the members of the pedigree. RESULTS: NGS has revealed that the two affected sisters both harbored homozygous c.1A>G variant of the GDAP1 gene, which caused replacement of the first amino acid Methionine by Valine (p.Met1Val). Their parents were both carriers of the heterozygous c.1A>G variant. The variant was unreported previously and has an extremely low frequency in the population. Meanwhile, one of the sisters and the mother also carried heterozygous c.710A>T variant of the BAG3 gene. CONCLUSION: The homozygous c.1A>G variant of the GDAP1 gene probably underlay the CMT in both children. Above result has enabled clinical diagnosis and genetic counseling for this pedigree.

Mitochondria-targeted antioxidant SkQ1 improves spermatogenesis in Immp2l mutant mice.

Previous studies have confirmed that spermatogenesis in homozygous Immp2l mutant male mice was normal at the age of 6 months, but was significantly abnormal at the age of 13 months. Meanwhile, oxidative stress is reported to be involved in spermatogenic impairment in old mutant mice. However, it is unclear whether antioxidant treatment is a suitable intervention for improving spermatogenesis in old mutant mice. This study sought to investigate the effect of mitochondria-targeted antioxidant SkQ1 on spermatogenesis in homozygous Immp2l mutant mice. Immp2l mutant mice were treated with the mitochondria-targeted antioxidant SkQ1 from the age of 6 weeks until 13 months. SkQ1 treatment significantly improved spermatogenesis in old Immp2 l mutant mice. Moreover, SkQ1 treatment improved the morphology of testicular seminiferous tubules, significantly reduced the apoptosis of germ cells and increased the level of GPX4 expression in old Immp2 l mutant mice. In conclusion, our data suggest that the mitochondria-targeted antioxidant SkQ1 is effective in improving spermatogenesis in Immp2 l mutant mice and might be used for the treatment of male infertility.

A complete Holocene record of trematode-bivalve infection and implications for the response of parasitism to climate change.

Increasing global temperature and sea-level rise have led to concern about expansions in the distribution and prevalence of complex-lifecycle parasites (CLPs). Indeed, numerous environmental variables can influence the infectivity and reproductive output of many pathogens. Digenean trematodes are CLPs with intermediate invertebrate and definitive vertebrate hosts. Global warming and sea level rise may affect these hosts to varying degrees, and the effect of increasing temperature on parasite prevalence has proven to be nonlinear and difficult to predict. Projecting the response of parasites to anthropogenic climate change is vital for human health, and a longer term perspective (10(4) y) offered by the subfossil record is necessary to complement the experimental and historical approaches of shorter temporal duration (10(-1) to 10(3) y). We demonstrate, using a high-resolution 9,600-y record of trematode parasite traces in bivalve hosts from the Holocene Pearl River Delta, that prevalence was significantly higher during the earliest stages of sea level rise, significantly lower during the maximum transgression, and statistically indistinguishable in the other stages of sea-level rise and delta progradation. This stratigraphic paleobiological pattern represents the only long-term high-resolution record of pathogen response to global change, is consistent with fossil and recent data from other marine basins, and is instructive regarding the future of disease. We predict an increase in trematode prevalence concurrent with anthropogenic warming and marine transgression, with negative implications for estuarine macrobenthos, marine fisheries, and human health.

Oocyte-Specific Expression of Mouse MEX3C652AA in the Ovary and Its Potential Role in Regulating Maternal Fos mRNA.

Currently, the human MEX3C gene is known to encode an RNA-binding protein of 659 amino acid residues. Here we show that the MEX3C gene has alternative splicing forms giving rise to multiple MEX3C variants, and some cells express MEX3C transcripts coding for short MEX3C isoforms but not transcripts for MEX3C(659AA) MEX3C(659AA) functions as an adaptor protein for Exportin 1 (XPO1)-mediated nuclear export since it increases the cytoplasmic distribution of poly(A)(+) RNA and since addition of the nuclear export signal (NES) sequence to a short MEX3C isoform MEX3C(464AA) confers similar cytoplasmic poly(A)(+) RNA accumulation activity as MEX3C(659AA) FOS mRNA is a potential MEX3C target mRNA. One mechanism by which MEX3C(659AA) could regulate FOS mRNA is by promoting its nuclear export. Overexpressing MEX3C(659AA) significantly increased FOS mRNA expression, whereas mutating the NES of MEX3C(659AA) and treating cells with leptomycin B to inhibit XPO1-mediated nuclear export attenuated FOS upregulation. FOS mRNA is unstable in somatic cells but less so in oocytes; how it is stabilized in the oocytes is unknown. Transcripts for the mouse counterpart of human MEX3C(659AA) (MEX3C(652AA)) are specifically expressed in developing oocytes in the ovary, although total Mex3c transcripts are expressed in both granulosa cells and oocytes. The specific expression of this long MEX3C isoform in oocytes and its ability to enhance FOS mRNA nuclear export and stability all suggest that MEX3C(659AA) is an RNA-binding protein that preserves maternal FOS mRNA in oocytes.

[Relationship between ERCC2 single nucleotide polymorphisms and male idiopathic infertility in Ningxia].

OBJECTIVE: To explore the influence of the DNA repair gene ERCC2 single nucleotide polymorphisms (SNPs) rs13181, rs1618536, and rs1799793 on male idiopathic infertility in Ningxia, China. METHODS: Using MassArray, we conducted a case-control study and genotyped three ERCC2 SNPs rs13181, rs1618536, and rs1799793 for 351 males (aged 31.0 +/- 4.2 years) with idiopathic infertility and another 327 normal fertile men (aged 33.0 +/- 5.9 years) as controls. RESULTS: The ERCC2 AnyG-anyA-anyA genotypes were significantly associated with an increased risk of idiopathic infertility (OR 0.414, 95% CI 0.176 - 0.970), while the three single ERCC2 SNPs rs13181, rs1618536, and rs1799793 showed no significant differences between the cases and controls (P > 0.05). CONCLUSION: The ERCC2 SNPs rs13181, rs1618536, and rs1799793 play a role of interaction in male idiopathic infertility in Ningxia, contributing to the risk of the disease.

Preparation and Photovoltaic Performance of a Composite TiO2 Nanotube Array/Polyaniline UV Photodetector.

TiO2 has great potential for application in UV photodetectors due to its excellent photoelectric response. In this work, composite nanomaterials of TiO2 nanotube arrays (TiO2 NTAs) and polyaniline (PANI) were successfully prepared on titanium sheets using an anodic oxidation electrochemical method. The results showed that the TiO2 NTA/PANI composite materials had excellent UV photosensitivity and responsiveness and good stability and reproducibility. This was mainly attributed to the p-n heterostructure formed inside the TiO2 NTA/PANI composites that hindered the recombination of photogenerated electron-hole pairs and improved their utilization of UV light. This work provides a theoretical basis for the application of metal oxides in UV photodetectors, which is important for the development of UV photodetectors.

Deep-fried Atractylodes lancea rhizome alleviates spleen deficiency diarrhea-induced short-chain fatty acid metabolic disorder in mice by remodeling the intestinal flora.

ETHNOPHARMACOLOGICAL RELEVANCE: Atractylodes lancea (Thunb.) DC. is a Chinese herb that has been commonly used to treat spleen-deficiency diarrhea (SDD) in China for over a thousand years. However, the underlying mechanism of its antidiarrheal activity is not fully understood. AIM OF THE STUDY: The antidiarrheal effects of the ethanol extract of deep-fried A. lancea rhizome (EEDAR) due to spleen deficiency induced by folium sennae (SE) were determined on the regulation of the short-chain fatty acid (SCFA) metabonomics induced by the intestinal flora. MATERIALS AND METHODS: The effects of EEDAR on a SE-induced mouse model of SDD were evaluated by monitoring the animal weight, fecal water content, diarrhea-grade rating, goblet cell loss, and pathological changes in the colon. The expression of inflammatory factors (tumor necrosis factor [TNF]-α, interleukin [IL]-1ß, IL-6, IL-10), aquaporins (AQP3, AQP4, and AQP8), and tight junction markers (ZO-1, occludin, claudin-1) in colon tissues were determined using quantitative polymerase chain reaction and western blotting. SCFA metabonomics in the feces of mice treated with EEDAR was evaluated using gas chromatography-mass spectrometry. Furthermore, 16S rDNA sequencing was used to determine the effect of EEDAR on the intestinal flora of SDD mice, and fecal microbiota transplantation (FMT) was used to confirm whether the intestinal flora was essential for the anti-SDD effect of EEDAR. RESULTS: Treatment with EEDAR significantly improved the symptoms of mice with SDD by inhibiting the loss of colonic cup cells, alleviating colitis, and promoting the expression of AQPs and tight junction markers. More importantly, the effect of EEDAR on the increase of SCFA content in mice with SDD was closely related to the gut microbiota composition. EEDAR intervention did not significantly improve intestinal inflammation or the barrier of germ-free SDD mice, but FMT was effective. CONCLUSION: EEDAR alleviated SE-induced SDD in mice, as well as the induced SCFA disorder by regulating the imbalance of the intestinal microbiota.

Atractyloside-A ameliorates spleen deficiency diarrhea by interfering with TLR4/MyD88/NF-κB signaling activation and regulating intestinal flora homeostasis.

PURPOSE: Spleen deficiency diarrhea (SDD) is one of the most common types of diarrhea and is linked to intestinal barrier dysfunction and intestinal flora disorders. Atractyloside-A (AA) is one of the main components of Atractylodes Lancea(Thunb.) DC., which acts on the gastrointestinal tract and has therapeutic effects on diarrhea. Folium sennae is a medicinal plant inducing diarrhea; thus, it is one of the effective methods to obtain a diarrhea model. However, the mechanism of action of AA in the treatment of SDD induced by Folium sennae is unclear. METHODS: The intestinal thrapeutic effect of AA on SDD in mice was evaluated by colon pathology. RNA sequencing (RNA-seq) was used to analyze the colonic transcriptome profiles. In addition, 16S rDNA sequencing and fecal microbiota transplantation (FMT) were carried out to verify the role of AA in the regulation of the intestinal flora. RESULTS: The findings revealed that AA alleviated SDD by ameliorating the pathological symptoms while suppressing intestinal inflammatory responses through the TLR4/MyD88/NF-kB signaling and reversing the impairment of mucin synthesis. Furthermore, AA improved the integrity of the intestinal barrier. RNA-seq identified 436 common DEGs out of 1033 DEGs between SDD and AA, and 1933 DEGs between SDD and Ctrl, which are highly enriched in the NF-κB and TNF pathways. Moreover, AA altered the composition of the intestinal flora and FMT reduced SDD. CONCLUSION: AA exerted a therapeutic effect on SDD through the regulation of the intestinal flora and the inflammation by interfering with the TLR4/MyD88/NF-κB signaling pathway.

Atractylodes lancea Rhizoma Attenuates DSS-Induced Colitis by Regulating Intestinal Flora and Metabolites.

Atractylodes lancea (Thunb.) DC. is a herb widely used traditionally for the treatment of gastrointestinal diseases such as gastric ulcer, spleen deficiency, and diarrhea. In China, people fry raw A. lancea (SCZ) together with wheat bran to make bran-fried A. lancea (FCZ). Ancient Chinese texts have documented that FCZ can enhance the function of regulating the intestines and stomach. Nevertheless, the effect and mechanism of SCZ and FCZ on ulcerative colitis (UC) are still unclear. The aim of this study was to compare the therapeutic effects of SCZ and FCZ and their mechanisms on dextran sulfate sodium (DSS)-induced UC in mice. The chemical constituents of SCZ and FCZ were analyzed using high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) with six reference compounds. The effects of SCZ and FCZ were investigated based on their effects on weight loss, disease activity index (DAI) score, colon length shortening, goblet cell loss, and pathological changes using the colons from a mouse model of DSS-induced UC. The effects of SCZ and FCZ on levels of the inflammatory cytokines (tumor necrosis factor-[Formula: see text], interleukin-6, interleukin-1[Formula: see text], mucoprotein (MUC2), tight protein (ZO-1, occludin), and the activation of macrophages were determined using immunohistochemistry (IHC) and immunofluorescence (IF). 16s RNA sequencing technology was used to detect the composition of the intestinal flora in each group. Nontargeted metabonomics was used to detect the serum metabolite levels of mice in each group. Pearson analysis was used to determine the correlation between the intestinal flora, metabolites, and pathological indices. Reverse transcription-polymerase chain reaction was used to detect the genes of different metabolite-related enzymes. A pseudogerm free (PGF) mouse model was used to verify whether the effect of SCZ and FCZ in UC depends on the regulation of intestinal flora. SCZ and FCZ could inhibit weight loss and decrease the DAI score, colon length shortening, goblet cell loss, and the extent of pathological changes in the colons of mice with DSS-induced colitis. Moreover, SCZ and FCZ inhibited the decrease in MUC2, ZO-1, occludin, production of pro-inflammatory factors, and activation of pro-inflammatory macrophages in colonic tissue. The effect of FCZ was better than that of SCZ. SCZ and FCZ not only inhibited the abundance of harmful bacteria and increased the abundance of beneficial bacteria, but also regulated the metabolism of disease-related metabolites such as amino acid and cholesterol metabolism. Both preparations inhibited the gene expression (Slc6A7, PRODH, Sdsl, HMGCR, SREBP-2) of different metabolite-related enzymes. In the PGF mouse model, the above effects were not observed. Rhizoma Atractylodes was effective in alleviating DSS-induced UC in mice, and FCZ was found to be superior to SCZ. The mechanism of action of FCZ and SCZ is mainly related to the regulation of intestinal flora and their associated metabolites.

Atractylenolide-1 targets SPHK1 and B4GALT2 to regulate intestinal metabolism and flora composition to improve inflammation in mice with colitis.

BACKGROUND: Atractylenolide-1, an active component of Atractylodes Lancea, which is widely used to improve the gastrointestinal function. However, the efficacy and mechanism remain unclear in treating ulcerative colitis (UC). PURPOSE: This study aimed to investigate the efficacy and the underlying mechanism of atractylenolide-1in UC. METHODS: A dextran sulfate sodium (DSS)-induced UC mouse model was used to investigate the efficacy of atractylenolide-1. 16S DNA sequencing, GC-MS technique and transcriptome sequencing were used to detect the composition of mouse intestinal flora, the changes of metabolites and gene expression in mouse intestine. Compound-reaction-enzyme-gene network was used to find drug targets. Recombinant plasmid overexpression was used to verify drug targets in DSS mouse models. RESULTS: The results showed that Atractylenolide-1 could significantly improve weight loss, diarrhea, blood in the stool, shortening of the colon, the loss of colonic goblet cells, reduction in mucoprotein MUC2, and tight junction proteins (zo-1, occludin) in mice with colitis. It reduced the inflammatory factors TNF-α, IL-6, IL-1ß as well. The 16S sequencing showed that Atractylenolide-1 regulated the diversity and abundance of the intestinal flora in mice with colitis, and the analysis of flora enrichment indicated that the regulation of intestinal flora by atractylenolide-1 may be related to the regulation of metabolism. Correlation analysis of metabolomics and transcriptome showed that two genes SPHK1 and B4GALT2 related to the metabolism of fructose and galactose were regulated by atractylenolide-1. Further verification showed that atractylenolide-1 significantly inhibited the aberrance of SPHK1 and B4GALT2 in the colon with colitis. Meanwhile, it inhibited the activation of the PI3K-AKT pathway. SPHK1 and B4GALT2 overexpressing reversed the therapeutic effect of atractylenolide-1 in mice with colitis. CONCLUSION: Atractylenolide-1 is a potential drug for the treatment of colitis by suppressing inflammation via the SPHK1/PI3K/AKT axis and by targeting SPHK1 and B4GAT2 to regulate fructose/galactose-related metabolism, thereby regulating the composition of the intestinal flora.

Comparative and phylogenetic analysis of complete chloroplast genomes from five Artemisia species.

Artemisia Linn. is a large genus within the family Asteraceae that includes several important medicinal plants. Because of their similar morphology and chemical composition, traditional identification methods often fail to distinguish them. Therefore, developing an effective identification method for Artemisia species is an urgent requirement. In this study, we analyzed 15 chloroplast (cp) genomes, including 12 newly sequenced genomes, from 5 Artemisia species. The cp genomes from the five Artemisia species had a typical quadripartite structure and were highly conserved across species. They had varying lengths of 151,132-151,178 bp, and their gene content and codon preferences were similar. Mutation hotspot analysis identified four highly variable regions, which can potentially be used as molecular markers to identify Artemisia species. Phylogenetic analysis showed that the five Artemisia species investigated in this study were sister branches to each other, and individuals of each species formed a monophyletic clade. This study shows that the cp genome can provide distinguishing features to help identify closely related Artemisia species and has the potential to serve as a universal super barcode for plant identification.

Pinocembrin inhibited cardiomyocyte pyroptosis against doxorubicin-induced cardiac dysfunction via regulating Nrf2/Sirt3 signaling pathway.

Doxorubicin (DOX) is a potent chemotherapeutic drug but the clinical use was limited by its dose-dependent cardiotoxicity. Pinocembrin (PCB), a flavonoid originally isolated from honeybee propolis and rhizomes of Boesenbergia pandurate displays diverse biological activities. However, the role of PCB in DOX-induced cardiac injury and its underlying molecular mechanism are not fully elucidated. The present study was designed to evaluate the protective role of PCB in a DOX-induced cardiotoxicity in vivo and in vitro. Our results revealed that PCB administration greatly improved cardiac function and reduced cardiac fibrosis manifested by LVEF, LVFS, LVIDd, LVIDs, and myocardial fibrotic area which were impaired by DOX treatment. The cardiac injury evidenced by LDH and CK-MB activities were reduced while the levels of IL-1ß and IL-18 were decreased following PCB treatment compared to DOX-treated mice. Mechanically, our present results showed that PCB significantly inhibited DOX-induced cardiomyocyte pyroptosis via activating Nrf2/Sirt3 signal pathway. Furthermore, the inhibition of Nrf2 in H9c2 cells abolished the protective role of PCB against DOX-induced cell toxicity, which was at least partly via upregulation of NLRP3-mediated pyroptosis. In conclusion, our study clearly demonstrated that PCB reduced cardiomyocyte pyroptosis to protect hearts from DOX-induced cardiotoxicity through activation of Nrf2/Sirt3 signal pathway.

Atractylodes oil alleviates diarrhea-predominant irritable bowel syndrome by regulating intestinal inflammation and intestinal barrier via SCF/c-kit and MLCK/MLC2 pathways.

ETHNOPHARMACOLOGICAL RELEVANCE: Atractylodes lancea (Thunb.) DC. is a widely used traditional herb that is well known for treating spleen deficiency and diarrhea. According to traditional Chinese medicine (TCM) theory, diarrhea-predominant irritable bowel syndrome (IBS-D) is caused by cold and dampness, resulting in diarrhea and abdominal pain. Nevertheless, the effect and mechanism of Atractylodes on IBS-D are still unclear. AIM OF THE STUDY: This study was designed to confirm the therapeutic effect of Atractylodes lanceolata oil (AO) in a rat model of IBS-D, and to determine the mechanisms by which AO protects against the disease. MATERIALS AND METHODS: The chemical components in AO were determined using gas chromatography-mass spectrometry (GC-MS). The expression levels of 5-hydroxytryptamine (5-HT), vasoactive intestinal peptide (VIP), and surfactant protein (SP) in serum and colon tissue were measured using enzyme-linked immunosorbent assay (ELISA). Reverse transcription-polymerase chain reaction (RT-PCR), western blotting (WB), immunohistochemistry (IHC), and immunofluorescence (IF) were used to elucidate the mechanism of action of AO toward inflammation and the intestinal barrier in a rat model of IBS-D. RESULTS: The 15 chemical substances of the highest concentration in AO were identified using GC-MS. AO was effective against IBS-D in the rat model, in terms of increased body weight, diarrhea grade score, levels of interleukin-10 (IL-10), aquaporin 3 (AQP3), and aquaporin 8 (AQP8), and reduced fecal moisture content, levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), 5-HT, VIP, and SP, while also reducing intestinal injury, as observed using hematoxylin-eosin (HE) staining. In addition, the results indicated that AO increased the mRNA and protein expression levels of stem cell factor (SCF) and c-kit and enhanced the levels of zonula occludens-1 (ZO-1) and occludin, as well as decreased the levels of myosin light chain kinase (MLCK) and inhibited the phosphorylation of myosin light chain 2 (p-MLC2). CONCLUSIONS: AO was found to be efficacious in the rat model of IBS-D. AO inhibited the SCF/c-kit pathway, thereby reducing inflammation and protecting against intestinal barrier damage via the MLCK/MLC2 pathway.

Atractylodin Attenuates Dextran Sulfate Sodium-Induced Colitis by Alleviating Gut Microbiota Dysbiosis and Inhibiting Inflammatory Response Through the MAPK Pathway.

In this study, we investigated the therapeutic effects and mechanism of atractylodin (ATL) on dextran sulfate sodium (DSS)-induced ulcerative colitis in mice. We found that atractylodin could significantly reverse the effects of DSS-induced ulcerative colitis, such as weight loss, disease activity index score; shorten the colon length, and reverse the pathological changes in the colon of mice. Atractylodin could inhibit the activation of colonic macrophages by inhibiting the MAPK pathway and alleviate intestinal inflammation in the mouse model of ulcerative colitis. Moreover, it could protect the intestinal barrier by inhibiting the decrease of the tight junction proteins, ZO-1, occludin, and MUC2. Additionally, atractylodin could decrease the abundance of harmful bacteria and increase that of beneficial bacteria in the intestinal tract of mice, effectively improving the intestinal microecology. In an LPS-induced macrophage model, atractylodin could inhibit the MAPK pathway and expression of the inflammatory factors of macrophages. Atractylodin could also inhibit the production of lactate, which is the end product of glycolysis; inhibit the activity of GAPDH, which is an important rate-limiting enzyme in glycolysis; inhibit the malonylation of GAPDH, and, thus, inhibit the translation of TNF-α. Therefore, ours is the first study to highlight the potential of atractylodin in the treatment of ulcerative colitis and reveal its possible mechanism.

Administration effects of single-dose GnRH agonist for luteal support in females undertaking IVF/ICSI cycles: A meta-analysis of randomized controlled trials.

The aim of the present meta-analysis was to evaluate the effects of the addition of single-dose gonadotropin-releasing hormone agonist (GnRHa) for luteal support on pregnancy outcomes in females partaking in in vitro fertilization or intracytoplasmic sperm injection cycles. In total, the studies were hand-searched from six electronic databases to compare the pregnancy outcomes between single-dose GnRHa administered as luteal phase support (GnRHa group) and regular luteal support (control group). In the GnRHa group, single-dose GnRH agonist were administered at 5/6 days after IVF/ICSI procedures. In the control group, single-dose GnRH agonist was not added during luteal phase support. Only randomized controlled trials were included. Sensitivity analysis was performed using Revman 5.3 software; the high heterogeneity identified in the present analysis was primarily caused by one study included. Following exclusion of this particular study, the meta-analysis results indicated significantly higher rates of ongoing pregnancy or live birth per transfer (P=0.002), clinical pregnancy per transfer (CPR; P=0.001) and multiple pregnancy per pregnancy (P=0.020) in the GnRHa group compared with those in the control group. Meta-analysis of a subgroup of trials with long-acting GnRH-a ovarian treatment protocols indicated that the rate of ongoing pregnancy or live birth (P=0.080), CPR (P=0.090) and multiple pregnancy per pregnancy (P=0.140) were not significantly different between the two groups. However, the results from trials that had used a multi-dose GnRH antagonist ovarian treatment protocol indicated a significantly higher ongoing pregnancy or live birth rate per transfer (P=0.010), CPR per transfer (P<0.0001) and multiple pregnancy rate per pregnancy (P=0.003) compared with those in the control group. The present results suggested that administration of single-dose GnRH agonist in the luteal phase may be an ideal choice for patients undergoing IVF/ICSI therapy.